We conducted a prospective, in silico imaging clinical trial to evaluate the feasibility and potential dosimetric benefits of computed tomography-guided stereotactic adaptive radiotherapy (CT-STAR) for the treatment of locally advanced pancreatic cancer (LAPC).Eight patients with LAPC received five additional CBCTs on the ETHOS system before or after their standard of care radiotherapy treatment. Initial plans were created based on their initial simulation anatomy (PCT-STAR was feasible in silico for LAPC and improved OAR and/or target dosimetry in 100% of fractions. Use of the PCT-STAR for the treatment of LAPC cancer proved feasible and was dosimetrically superior to non-adapted CT-stereotactic body radiotherapy.